Luminal hydrochloric acid stimulates rapid transepithelial ion fluxes in rodent esophageal stratified squamous epithelium.
It remains unclear whether enhanced ion fluxes occur in the esophageal stratified squamous epithelium upon acid exposure. Rat esophageal tissues devoid of submucosal glands displayed basal short-circuit current (Isc) of 5.03 +/- 1.93 microA/cm(2) and lumen-negative potential difference (PD) in association with net absorption of Na+ and Cl-, and secretion of HCO3(-). Luminal hydrochloric acid (HCl) challenge (pH = 1.6) triggered an acute rise of the Isc and increment of negative PD to seven-fold of baseline, which was diminished in HCO3(-)-free, but not Na+- free buffer. The rise of Isc was inhibited by pretreatment with di-isothiocyanatostilbene-2, 2'-disulphonic acid (DIDS) and 5-(N-ethyl-N-isopropyl)-amiloride (EIPA). Topical carbachol, capsaicin, forskolin or CFTR(inh)-172 had no effect on basal Isc.CFTR(inh)-172 did not reduce the acid-increased Isc. Functional ablation of capsaicin-sensitive nerves had no effect on the acid-induced Isc. The phenomenon of enhanced ion fluxes upon acid stimulation was confirmed in human esophageal specimens. Our results demonstrated that the mechanism of acid-induced rapid transepithelial ion fluxes is dependent on the presence of bicarbonate ions as well as functional anion transporters and Na+/H+ exchanger, but independent of cystic fibrosis transmembrane conductance regulator (CFTR). The capsaicin-sensitive and muscarinic-dependent nerve pathways did not play roles in the mechanism.
Lin
B R
BR
Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan.
Hsieh
H T
HT
Lee
J M
JM
Lai
I R
IR
Chen
C F
CF
Yu
L C H
LC
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000293:Adolescent; D000368:Aged; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017776:Autonomic Pathways / Q000187:drug effects / Q000502:physiology; D001639:Bicarbonates / Q000737:chemistry; D002021:Buffers; D002211:Capsaicin / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000494:pharmacology; D015194:Diffusion Chambers, Culture; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism*; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006851:Hydrochloric Acid / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007477:Ions / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009475:Neurons, Afferent / Q000187:drug effects; D010275:Parasympathetic Nervous System / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors
D001639:Bicarbonates; D002021:Buffers; D007477:Ions; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000584:Amiloride; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D006851:Hydrochloric Acid; D002211:Capsaicin; C039614:ethylisopropylamiloride